AbbVie's antibody drug conjugate (ADC) Temab-A has demonstrated promising efficacy in patients with EGFR-mutated non-small cell lung cancer (NSCLC), achieving a 63% overall response rate in a Phase I trial presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.
The drug, internally designated as ABBV-400, showed activity in patients with advanced EGFR (epidermal growth factor receptor)-mutated, non-squamous NSCLC who had progressed after platinum-based chemotherapy doublet and tyrosine kinase inhibitor treatments. Temab-A was administered every three weeks, with patients initially enrolled at 3 mg/kg before the dose was reduced to 2.4 mg/kg.
Clinical Trial Results
Data from 41 patients enrolled in the Phase I trial (NCT05029882) demonstrated a median duration of response of 9.8 months and a median progression-free survival of 10.9 months. These results were observed irrespective of c-Met expression levels, the protein targeted by Temab-A's mechanism of action.
The ADC works by targeting c-Met and delivering a topoisomerase 1 inhibitor payload to cancer cells. According to Dr. Nivedita Aanur, NSCLC clinical lead at AbbVie, the data "demonstrate a manageable safety profile, promising anti-tumour activity and are supportive of further exploration of this novel ADC in this setting."
Safety Profile
Treatment-emergent adverse events occurred in all patients, with the most common being hematologic and gastrointestinal side effects. Serious events of grade 3 and higher occurred in 78% of patients. Consistent with other ADCs in the class, interstitial lung disease was observed in 7% of participants.
Market Context
The results come as the NSCLC market continues to expand, with GlobalData projecting growth from $30.7 billion in 2021 to $45.4 billion by 2031. Nearly 85% of lung cancers are NSCLC, with initial treatment for patients with EGFR mutations typically including targeted therapy and/or chemotherapy.
Currently approved immunotherapies in the market include MSD's Keytruda (pembrolizumab), Bristol Myers Squibb's Opdivo (nivolumab), and Roche's Tecentriq (atezolizumab). The only ADC currently approved for NSCLC is Daiichi Sankyo and AstraZeneca's Enhertu (trastuzumab deruxtecan), which received approval in the US and Europe in 2022 and 2023 respectively.
Enhertu, approved for HER2-mutant NSCLC, previously demonstrated an objective response rate of 49%, making direct comparisons with Temab-A's results in EGFR-mutated patients difficult. However, immunotherapies are generally not recommended as first-line treatments for patients with EGFR mutations.
Development Pipeline
Aanur noted that Temab-A "has now shown anti-tumour activity in both wild-type and EGFR-mutant advanced NSCLC, demonstrating its potential in these molecularly diverse populations. With its best-in-class potential, we believe Temab-A may offer meaningful patient impact compared to current standards of treatment."
The drug is also being evaluated in a Phase I/II trial (NCT06772623) as a first-line treatment for NSCLC without actionable genomic alterations in combination with AbbVie's investigational programmed cell death 1 inhibitor budigalimab. Additionally, AbbVie is conducting separate Phase II (NCT06107413) and Phase III studies (NCT06614192) with Temab-A for colorectal cancer indications.
The Phase I trial is enrolling approximately 500 adults with NSCLC, gastroesophageal adenocarcinoma, colorectal cancer, or advanced solid tumors. AbbVie also has another c-Met-targeting ADC, Teliso-V (telisotuzumab vedotin), which uses a different payload and is FDA-approved under the brand name Emrelis for adults with locally advanced or metastatic, non-squamous NSCLC with high c-Met protein overexpression who have received prior systemic therapy.
